Evaluation of Two Pain Assessment Methods (Tactile and Air blast) for Comparison the Effectiveness of Nd:YAG Laser Therapy and Non-Laser Therapy on Dentin Hyper Sensitivity Treatment: A Systematic Review and Meta-analysis

Statement of the Problem: Dentin hypersensitivity (DH) is a common irritating condition. A precise sensitive test for its assessment can greatly aid in appropriate treatment planning. Purpose: This meta-analysis aims to compare the air blast and tactile tests for assessment of the efficacy Nd:YAG laser therapy versus non-laser treatments for DH in short-term and long-term follow-ups. Materials and Method: For this review, an electronic search of the literature was carried out in three databases by two researchers for English articles published until March 10, 2021. Pooling of the data extracted from the selected articles was performed according to the PRISMA statement by the random-effect model. The mean difference (MD) and 95% confidence interval (CI) of pain score before the treatment onset and during the follow-up period according to the visual analog scale (VAS) were calculated. The level of heterogeneity was assessed by the I2 test, and a funnel plot was drawn to assess the publication bias of the reviewed studies. Results: Of 152 articles primarily retrieved, 9 randomized clinical trials (RCTs) using the air blast test and 4 RCTs using the tactile test were subjected to quantitative synthesis. In the short-term follow-up and immediately after treatment, the air blast test showed superiority of laser therapy compared with non-laser treatments (SMD: 0.55, 95% CI: 0.05-1.04, p= 0.03). However, this difference was not significant according to the tactile test (SMD: 0.48. 95% CI: 0.01-0.96, p= 0.06). In the long-term follow-up, the difference between laser therapy and non-laser modalities was not significant according to both air blast (SMD= -0.38, 95% CI: -1.43-0.67, p= 0.48) and tactile (SMD=0.0, 95% CI: -0.38-0.38, p= 0.99) tests. Conclusion: Comparison of laser therapy and non-laser modalities in the short-term reveal-ed higher sensitivity of the air blast test due to its mechanism of action compared with the tactile test. Further studies are required to interpret the results in the long-term follow-up.


Introduction
Dentin hypersensitivity (DH) refers to a transient sharp pain in exposed dentin following external stimulation by thermal, electrical, mechanical, tactile, chemical, or osmotic stimuli, or evaporation. Pain due to DH cannot be attributed to any other reason. Cold is the most common trigger for DH [1].
Root exposure due to gingival resorption followed by periodontal disease is one of the most common causes of this problem. New evidence indicates that the mechanism of DH pain can be explained by combination of hydrodynamic theory and neural theory. This can be explained that because of the abovementioned stimuli, the movement of dentinal fluid changes the intrapulpal pressure around odontoblasts and their odontoblastic processes, which leads to stimulation of intradental myelinated A-β and A-δ fibers, resulting in generation of a transient sharp pain [2-3]. High prevalence and irritating nature of DH, and high risk of diagnostic errors can lead to its misdiagnosis, for instance with the symptoms of dental caries, and subsequent aggressive treatments. Air blast (evaporation), cold water, thermal and tactile stimuli, and subjective examination can be used for the assessment and identification of pain, and evaluation of the efficacy of different treatments for DH. Each test employs a specific stimulus for pain induction, such as mild air stream of air spray in air blast test, the tip of a probe in tactile test, and ice in thermal stimulation test [1,4]. Of the abovementioned tests, the air blast and tactile tests are more commonly used for the assessment of DH due to their physiological nature and reproducibility [5]. Nonetheless, selection of a precise and reliable test for assessment of the efficacy of treatments is a challenge for dental clinicians because in absence of a precise and sensitive test, accurate treatment planning would not be possible. Thus, selection of a reliable test is a fundamental step in assessment of treatment efficacy. The mechanism of action of these tests is based on the movement of dentinal fluid and stimulation of odontoblastic processes [6]. Thus, the efficacy of the available treatment modalities for DH such as topical desensitizing agents and laser therapy, which are based on sealing of dentinal tubules and reduction of the movement of dentinal fluid and stimulation of odontoblastic processes, can be well evaluated by these tests [7]. Of the available treatments for DH, topical desensitizing agents are the most affordable, widely accessible, and most frequently used modalities. However, their effects are short-term since the deposits sealing the tubules are removed over time due to the consumption of acidic foods and drinks, and tooth brushing [6][7]. Therefore, laser therapy with CO2, Er, Cr:YSGG, Er:YAG, Nd:YAG and GaAlAs lasers were suggested for treatment of DH. Depending on the type and wavelength of laser, laser therapy can have a success rate of 5.2% to 100% for treatment of DH [8]. The effectiveness of different lasers in reducing the diameter of dentin tubules has been proven [9]. Among them, Nd:YAG laser has shown the highest efficacy for resolution of DH due to the melting of hydroxyapatite crystals, fusing and re-solidification of dentin along with analgesic properties causing no damage to teeth structure [10][11][12]. However, a comprehensive treatment for DH has yet to be introduced. Substantial variations in selection of a precise test for assessment of DH, study designs, and frequency, duration and time interval of follow-up sessions are factors that need to be taken into account in review studies and meta-analyses on DH.
Previous studies that used these tests to compare the efficacy of laser-and non-laser treatments for DH with different follow-up periods have reported controversial results [13][14][15][16], which can be due to the differences in pain assessment tests, assessment time points, variable study designs, and use of different scales. Some metaanalyses on different tests combined the results of randomized clinical trials (RCTs) to compare the efficacy of laser and non-laser treatment modalities based on visual analog scale (VAS) or visual rating scale (VRS) scores [11,17]. However, such studies have numerous methodological flaws such as absence of precise inclusion criteria, use of different teeth in different studies, various follow-up periods, different assessment scales (VAS or VRS), using different tests (tactile, air blast, or thermal stimulation), and high heterogeneity; all these factors can contribute to unreliable results. Some metaanalyses combined the results of different tests [11,18]; while the stimulation threshold might be variable for different tests because each test works based on a particular stimulus.
A recent systematic review evaluated the efficacy of different laser types for treatment of DH in comparison with non-laser modalities and placebo by combining the results of different tests, and found no significant difference between laser and non-laser modalities. However, the best results were obtained when both types of treatments were combined. Moreover, among the tested laser types, Nd:YAG laser showed the highest efficacy [11].
This study showed that different tests are suitable for assessment of the efficacy of laser treatments. However, combining the results of different tests, not differentiating between different laser types and absence of longterm follow-ups necessitate further securitization of this topic. A recent meta-analysis evaluated the use of air blast test to compare the efficacy of Nd:YAG and diode lasers versus desensitizing agents for treatment of DH over different follow-up periods. However, they combined the results of the two laser types and did not assess the results in the long-term, which highlights the need for more comprehensive studies on this topic [17].
It appears that using an accurate and reliable test can increase the validity of RCT and systematic reviews to eliminate the ambiguities regarding the accuracy of the results of equivocal studies. Therefore, a comprehensive targeted study is required to find the most effective test for assessment of DH. This meta-analysis aims to compare two commonly used tests for assessment of DH namely the air blast and tactile tests to compare the efficacy of Nd:YAG laser therapy and non-laser modalities for treatment of DH in the short-term and long-term.

Materials and Method
This systematic review and meta-analysis was conducted in accordance with the PRISMA, Cochrane Collaboration, and Check Review checklists.

Focused Clinical Question
What is the difference between the tactile and air blast pain assessment tests for evaluation of the efficacy of Nd:YAG laser and non-laser treatments for DH in the short-term and long-term follow-ups? The following studies were excluded:  In vitro and animal studies, review articles, and unpublished manuscripts  Studies on patients with postoperative DH after procedures such as bleaching, periodontal treatment, and restorative procedures  Use of VRS or SCASS for assessment of pain  Use of probe stimulation, cold water, or thermal stimuli to induce pain  Not reporting baseline data in the study  Full-text in a language other than English

Data Extraction
Two independent reviewers (ZB and MK) evaluated the selected studies and the following information was extracted including title of the study and the first author's name, publication year, country, study design, number of participants, details of intervention and control groups, follow-up times, assessment methods, and the air blast and tactile test scores in both the intervention and control groups. Data were analyzed by two researchers and in case of disagreement a third reviewer was consulted.

Outcome Measurement
Any changes in the mean VAS pain score in air blast and tactile tests during the follow-up sessions compared with baseline in laser and non-laser groups were calculated.

Risk of Bias and Assessment of the Quality of Evidence
Two masked reviewers conducted qualitative assessment of the methodology of the selected RCTs according to the Consolidated Standards of Reporting Trials.
The following criteria were evaluated including random sequence generation, allocation concealment, blinding of participants and personnel, blinding of assessors, incomplete outcome data reporting, selective outcome reporting, and other sources of bias [18][19][20].
Comprehensive assessment of the risk of bias of studies was conducted according to the following criteria: High risk of bias: studies that were rendered highrisk in at least one item Unclear risk of bias: Studies that had unclear risk of bias in one or more items

Data Synthesis and Statistical Analyses
The mean VAS pain scores extracted from RCTs in air blast and tactile tests in different follow-up sessions were entered into a database. The heterogeneity of the studies was evaluated by the I 2 test and p≤ 0.05 was considered statistically significant. Since the follow-up sessions had been conducted at different time points, subgroup analyses were performed according to different follow-up times to decrease heterogeneity. In addition, the effect size was calculated by using the mean difference (MD) and 95% confidence interval (CI), and the risk difference (95% CI) was also calculated for

Description of Studies
Nine selected RCTs had two arms comparing laser and non-laser treatment modalities. Accordingly, 606 patie- group. VAS was used in all studies to assess the level of pain at baseline, after the treatment, and during the follow-up sessions. Table 1 presents the main characteristics of RCTs evaluated in this study in brief. Figure 2 shows the result of quality assessment of the articles. None of the studies met all the evaluated criteria. Randomization of samples was questionable in four studies [15,[40][41][42]. Allocation concealment was not disclosed in five studies [15,38,[40][41][42]. Blinding of participants and personnel was not clear in four studies [14,16,40,42]. Blinding of outcome assessment was not disclosed in two studies [40,42] and was negative in two studies [38,43]. Thus, seven studies had unclear risk of bias while two studies had high risk of bias since the outcome assessment was not performed blindly.

Outcomes of Meta-analysis
Since the results of tactile and air blast tests for pain assessment had been reported at different follow-up sessions in the reviewed studies, data analysis for the two tests was performed separately as subgroup analyses at diffe-

Long-term Effect
The results at 9 to 18-month follow-ups in the air blast test were considered as the long-term results, and indic-  In the tactile test, the results at 6 to 18-month follow-ups were evaluated, which similar to the air blast t-est, showed no significant difference between the two treatment groups. This analysis was performed on 80 patients across two studies (SMD=0.0, 95% CI: -0.38-0.38, p=0.99) (Supplementary Figure 6).

Publication Bias
In the present study, the tests to determine asymmetry for assessment of publication bias were performed on follow-up data immediately after treatment. Only one study by Chebel et al. [16] did not report the data immediately after treatment and due to the lack of high sensitivity between the data obtained at different time points, the data at one week after treatment was replaced (Supplementary Figure 7). Accordingly, the results of the funnel plot analysis of DH following laser and nonlaser treatments did not show any asymmetry. Even in    Table 2).

Discussion
This meta-analysis compared the efficacy of two pain  However, the tactile test showed the superiority of laser therapy only at 1 week and 1 month, and the results immediately after treatment were not significant (similar to the long-term results), which was unexpected. This can be due to the different efficacy of treatments and the mechanism of action of the two pain assessment tests.
In terms of efficacy of different treatment modalities, it should be mentioned that the mechanism of effect of all non-laser modalities evaluated in this study on DH is the same either through obstruction of the exposed dentinal tubules or by desensitization of the pulpal nerves [44]. Potassium-containing desensitizing agents prevent the conduction and transfer of nerve signals from the nerve terminal of dental pulp by inhibition of nerve cell repolarization, and do not obstruct the dentinal tubules [42,45]. Other desensitizing agents physically seal the dentinal tubules by deposition of crystals (first mechanism). However, evidence shows that the depos-  [42,46]. In addition, coagulation of proteins in dentinal fluid following laser therapy causes further occlusion of dentinal tubules, decreases their permeability, and consequently decreases the movement and flow of dentinal fluid [42]. Therefore, it appears that simultaneous analgesic effect and tubular obstruction by  to laser therapy for DH. This is because in addition to its higher efficacy, it is more affordable and more easily accessible than laser, and its application is simpler than laser therapy for both the clinician and patient [13].
Furthermore, considering the positive and negative aspects of each method, the application of laser combined with non-laser treatments such as CPP-ACPF or Gluma desensitizer, besides their individual benefits, can overcome these limitations. It seems that their use in combination has additive effects in the treatment of DH.
The effectiveness of this combined approach has been proven in various studies with the greatest effect in improving patients' pain [9,13,[49][50].
In addition to the assessment of the efficacy of laser

Conclusion
The current results indicated the comparable efficacy of Nd:YAG laser therapy and topical desensitizing agents for reduction of DH according to both air blast and tactile tests. Nonetheless, the air blast test had higher sensitivity for assessment of treatment results in the shortterm compared with the tactile test due to its particular mechanism of action and more severe stimulation of a higher number of open dentinal tubules. However, interpretation of the results of the long-term follow-ups requires further investigations.